Intro to Endocrinology Flashcards
What are the three types of hormones?
peptide-protein
lipid
nonpeptide amino acid-based
True or false: hormones exert their effect only when they reach a high concentration.
false - work at very low concentrations
What are the three general types of effects hromones can have?
endocrine
paracrine
autocrine
What do free hormone need to bind to?
carrier proteins in the serum and free receptor to make a hormone-receptor complex (which does the actual signalling)
True or false: hormone-receptor binding is irreversible.
false - it’s reversible
but note that some of the drugs we use to counter this system are irreversible
Since there are only a limited number of receptors on a cell, the receptors are _____
saturable
Why can se way that hormones and receptors have varying levels of specificity?
because they may bind to multiple receptors with varying specificity and a given receptor may bind multiple hormones
the key is the varying specificity - the one with the highest specificity will get the strongest signal
What is the integrating controller of the endocrine system?
hypothalamus
What does the hypothalamus control?
pituitary gland, which then controls all the rest
What are the other endocrine glands?
pancreas, thyroid, parathyroid, adrenals, ovaries and testes
What part of the pituitary is a true endocrine gland and what is an extension of neural tissue?
anterior is the true endocirne gland of epithelial origin
the posterior is an extension of the neural tissue
What project into the posterior pituitary to trigger release of hormone?
hypothalamic neurons
What hormones are produced by those hypothalamic neurons in the posterior pituitary?
oxytocin and vasopressin
What is the advantage for this arrangement between the hypothalamus and posterior pituitary?
target cells see the stimulatory hormone very quickly - hugely important for both vasopressin and oxytocin
How is the axis arranged for the anteiror pituitary?
- hypothalamic nueonrs deposit hormones into the hypothalamo-hypophyseal portal system
- this system will bathe the pituitary cells in those hormones and hormones will bind appropriate receptors
- Ant pit cells will produce and release their hormone into general circulation
So is this slower or faster than with ht eposterior pit?
slower
Is most of the regulation of the hormone secretion negative or positive?
negative feedback
e.g., thyroid hormone curtails release of thyroid releasing hormone and thyroid stimulating hormone
Positive feedback is rare in this system, but what is an example?
snow ball effect from very high ovarian estrogen stimulating ovulation
What are the three groups of non-peptide amino acid derivatives?
thyroid hormones
catecholamines
tryptophan derivatives like melatonin
What are the two general lipid hormones
steroids and eicosanoids
In general how are protein/peptide hormones synthesized?
a preprohormone is synthesized and cleaved into prohormone in the RER
the prohormone goes to the golgi where further enzymatic cleavage occurs to produce th e mature hormone
it’s then packaged into secretory granules
In general, how are peptide hormones secreted?
upon apropriate signals, the secretory granules fuse with plasma membrane, releasing the hormone into the circulation
are protein hormones soluble in water?
yes
What’s the usual carrier protein that will carry and increase the total amount of hormone in the circulation
albumin
Preprohormone for TRH is efficient because….
it’s cleaved down to 5-6 copies of TRH
In genera, how are steroid hormones synthesized?
derived from cholesterol
converted to findal product by enzymatic action
enzymes are located in the mitochondria and smooth ER
Is the steroid packaged and stored before it’s secreted?
nope - it’s produced and secreted right away
Are steroid hormones soluble in water?
nope, so 99.9% will be bound to a transport protein
What are most of the eicosanoids derived from?
arachidonic acid
What enzyme will form the prostaglandins and thromboxanes?
cyclooxygenase
What enzyme makes leukotrienes?
lipoxygenase
What enzyme will make the epoxides?
cytochrome p450 mono-oxygenase
Do eicosanoids work locally or at a distance?
only locally (and at low levels)
What are three examples of catecholamines?
dopamine
norepinephrine
epinephrine
What kind of receptor do the catecholamines bind to?
G-protein couple transmembrane receptors
What are the two thyroid hormones?
T4 (thyroxine0
T3 (Triiodothyronine)
In general, how is thyroid hormone synthesized?
syntesized on a protein backbone which is processed in lysosomes
Control of production for thyroid hormone is based on what?
whehter the enzymes are available and iodine availability
What are the two main groups of Tyrosine-based hormones?
catecholamines and thyroid hormones
What are the two main Tryptophan-based hormones?
serotonin and melatonin
What are the ways in which hormone signaling can be down-regulated?
- decrease receptor number
2. increase dgradation of the hormone in cells
What are the ways in which hormone signalling can be up-regulated?
- increasing receptor number
2. decreasing intracellular degradation of hormone
Where is the receptor for protein/peptide hormones?
in the cell membrane of the target cells
What kind of kinase are protein hormone receptors often? WHat are the majority though?
tyrosine kinase
most activate secondary messengers like GPCRs
WHat are three ways these G proteins can transduce signaling cascades?
- stimualtes adenylate cyclase to produce cAMP
- increase cytoplasmic calcium
- Activate phospholipase C to produce DAG and IP3
Specifically which G protein is usually activated by protein hormones?
Gs-alpha
What is the signalling pathway for Gs-alpha?
- activates adenylate cyclase
- increases produciton of cAMP
- cAMP activates PKA
- PKA phosphorylates lots of targets
What family are the steroid receptors in?
nuclear receptor superfamily
Describe the sequence at the binding site for the steroid receptors (the hormnoe binding response element)?
it’s a palindrome
What are the steroid hormone receptor ligands we care about?
estrogens progesterones androgens glucocorticoids mineralocorticoids
What kind of receptor family is used by thyroid hormone?
RXR heterodimers
unliganded RXR binds liganded receptor
What is the main substrate in a liganded RXR homodimer system?
all trans retinoic acid
Describe the transcriptional activation of RXR:TR heterodimer by thyroid hormone.
- the RXR and TR are bound to the hormone response element with a transcriptional corepressor
- transcription co-repressor is released when the T3 binds to the TR
- a transcription co-activator binds to the hormone receptor heterodimer complex
- transcrpition is modulated
Hormones are degraded by liver and kidney metabolism. Speciically what happens to steroid hormones?
oxidation by liver cytochrom p450 (phase 1)
Why is pulsatile secretion of hypothalamic and pituitary hormones required?
prevents desensitiztaion of the downstream hormone receptors
importance because continuous administration of these hormones would down-regulate the hormone receptors and thus reduce hormone signaling
What about a sleep cycle will requires adjustment of when to take blood samples to evaluate someones hormone levels?
hypothalamic hormone secretion has a circadian rhythm of secretion
What does it mean for a hormone to be permissive?
it allows another hormone to exert it’s full effect
Which would icnrease signalling more - an additive or synergistic relationship?
synergistic
